The objective of this study is to formulate bioadhesive microparticulate to deliver levodopa into the brain which could significantly improve the bioavailability. The microspheres of gelatin were prepared by surface polymerization using glutaraldehyde as a crosslinking agent. Central composite design (CCD) was employed to optimize the formulation parameters of levodopa microsphere for maximum swelling index, drug content, time of drug release, percentage drug release, size of the microspheres and bioadhesivity by using polynomial regression model. The quantitative effect of the formulation factors (viz. drug:polymer ratio, agitation speed, glutaraldehyde concentration) at different levels on bioadhesion and drug release were predicted using polynomial equations. Following optimization a formulation comprising of levodopa: gelatin ratio 1:1.98 and glutaraldehyde 32.42μl at 2200rpm was identified for maximizing bioadhesivity and obtaining sustained drug release. The optimal microsphere preparation was subsequently characterized in terms of size (11 μm), drug loading (95%), swelling index (3.5), drug release (99.7% at 4.5hr), in vitro bioadhesion (95%) and release kinetics. Kinetic models revealed that drug release followed anomalous (non-Fickian) diffusion. Predicted values of final optimized formula were very close to actual values which confirmed practicability and validity of the model. Hence levodopa-microspheres as reservoirs for nasal delivery were successfully formulated and optimized CCD.